Search results for: Stepped Cascade weir

Authors: Sharvari Sane, Swati Sharma, Sanjay K. Prasad

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Local trains are the lifelines of Mumbai city. Earlier 1500 Volt D.C. supply, is now completely and successfully converted into 25 KV A.C. in central, western and harbour routes. This task is the outcome of the advancement in the area of power electronics. Author has already done the comparative study between D.C. and A.C. supply of traction and predicted the serious problem regarding the harmonics. In this paper, the simulation for 5 level as well as 7 level multilevel inverter has been done which is the substitute for the present cascade type inverter. This paper also showed the reduced level of Total Harmonic Distortion (THD) in the traction system.

Keywords: total harmonic distortion (THD), traction sub station (TSS), harmonics, multilevel inverter

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Authors: Kuen-Ming Shu, Jyun-Wei Chen

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Encapsulated O-rings are specifically designed to address the problem of sealing the most hostile chemicals and extreme temperature applications. Ultrasonic vibration hot embossing and ultrasonic welding techniques provide a fast and reliable method to fabricate encapsulated O-ring. This paper performs the design and analysis method of the acoustic horns with double extrusion to process tube double side flange simultaneously. The paper deals with study through Finite Element Method (FEM) of ultrasonic stepped horn used to process a capsulated O-ring, the theoretical dimensions of horns, and their natural frequencies and amplitudes are obtained through the simulations of COMOSOL software. Furthermore, real horns were fabricated, tested and verified to proof the practical utility of these horns.

Keywords: encapsulated O-rings, ultrasonic vibration hot embossing, flange making, acoustic horn, finite element analysis

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Authors: M. Münch, R. Brandt

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Martensitic steels with an ultimate tensile strength beyond 2000 MPa are applied in the powertrain of vehicles due to their excellent fatigue strength and high creep resistance. However, the creep controlling mechanism in martensitic steels at ambient temperatures up to 423 K is not evident. The purpose of this study is to review the low temperature creep (LTC) behavior of martensitic steels at temperatures from 363 K to 523 K. Thus, the validity of a logarithmic creep law is reviewed and the stress and temperature dependence of the creep parameters α and β are revealed. Furthermore, creep tests are carried out, which include stepped changes in temperature or stress, respectively. On one hand, the change of the creep rate due to a temperature step provides information on the magnitude of the activation energy of the LTC controlling mechanism and on the other hand, the stress step approach provides information on the magnitude of the activation volume. The magnitude, the temperature dependency, and the stress dependency of both material specific activation parameters may deliver a significant contribution to the disclosure of the nature of the LTC rate controlling mechanism.

Keywords: activation parameters, creep mechanisms, high strength steels, low temperature creep

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Authors: Michel Kulhandjian, Dimitris A. Pados

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The objective of this work is to develop a theoretical framework for reliable digital recording system identification from digital audio files alone, for forensic purposes. A digital recording system consists of a microphone and a digital sound processing card. We view the cascade as a system of unknown transfer function. We expect same manufacturer and model microphone-sound card combinations to have very similar/near identical transfer functions, bar any unique manufacturing defect. Input voice (or other) signals are modeled as non-stationary processes. The technical problem under consideration becomes blind deconvolution with non-stationary inputs as it manifests itself in the specific application of digital audio recording equipment classification.

Keywords: blind system identification, audio fingerprinting, blind deconvolution, blind dereverberation

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Authors: Ömer Ateş, Atilla Savaş

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Reducers and transmission systems are power and speed transfer tools that have been used for many years in the technology world and in all engineering fields. Since today's transmissions have a threaded tap system, torque interruption occurs during tap change. besides, breakdown and manufacturing costs are high. Another problem is the limited torque and rpm setting in stepped gearbox systems. In this study, a new type of transmission system is designed to solve these problems. This new type of transmission system has been called the Continuously Variable Pulley. The most important feature of the transmission system in the study is that it can be adjusted Revolutions Per Minute-wise and torque-wise at the millimeter (precision) adjustment level. In order to make adjustments at this level, an adjustable pulley with the help of hydraulic piston is designed. The efficiency of the designed transmission system is 97 percent, the efficiency of today's transmissions is in the range of 85-95 percent. examined at the analysis and calculations, it is seen that the designed system gives realistic results and can be compared with today's transmissions and reducers. Therefore, this new type of transmission has been proven to be usable in production areas and the world of technology.

Keywords: gearbox, reducer, transmission, torque

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Authors: F. Sallem, B. Dahhou, A. Kamoun

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In this work, the main problem considered is the detection and the isolation of the actuator fault. A new formulation of the linear system is generated to obtain the conditions of the actuator fault diagnosis. The proposed method is based on the representation of the actuator as a subsystem connected with the process system in cascade manner. The designed formulation is generated to obtain the conditions of the actuator fault detection and isolation. Detectability conditions are expressed in terms of the invertibility notions. An example and a comparative analysis with the classic formulation illustrate the performances of such approach for simple actuator fault diagnosis by using the linear model of nuclear reactor.

Keywords: actuator fault, Fault detection, left invertibility, nuclear reactor, observability, parameter intervals, system inversion

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Authors: Yan Rongxin, Sun Wei, Li Weidan

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Based on the acoustics cascade sound theory, the mechanism of air leak sound producing, transmitting and signal detecting has been analyzed. A formula of the sound power, leak size and air pressure in the spacecraft has been built, and the relationship between leak sound pressure and receiving direction and distance has been studied. The center frequency in millimeter diameter leak is more than 20 kHz. The situation of air leaking from spacecraft to space has been simulated and an experiment of different leak size and testing distance and direction has been done. The sound pressure is in direct proportion to the cosine of the angle of leak to sensor. The portable ultrasonic leak detector has been developed, whose minimal leak rate is 10^-1 Pa·m³/s, the testing radius is longer than 20 mm, the mass is less than 1.0 kg, and the electric power is less than 2.2 W.

Keywords: leak testing, manned spacecraft, sound transmitting, ultrasonic

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Authors: Siavash Soltani Hemmat

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Although 21st-century humanity is at the height of technology and has stepped toward the endless boundaries of knowledge, there are still people in many parts of the world who are deprived of even the most fundamental freedoms. Whereas without freedom, no possible meaning can be imagined for human life, none of the human talents will have the chance to flourish, and that man will be reduced to the level of an animal, removing the obstacles to human freedom, especially from the viewpoint of thoughts, is of utmost importance, in which the liberal ideas of the modern centuries have played an incomparable role. The aim of the present study is to introduce and explain the liberal ideas in the modern centuries and their role in the expansion of human freedoms in order to weaken and discredit the ideological and intellectual barriers to restricting the freedom of individuals and to pave the way for the liberation of humanity. A descriptive method has been employed in order to achieve the objectives of the research. Besides, for data collection, a library method has been conducted. In this study, three ideological teachings of the social contract , resistance against unjust governance and natural law were recognized as the foundations of the realization of fundamental freedoms of the people in the modern centuries and their content was explained and examined.

Keywords: freedom, natural law, social contract, resistance

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Authors: Gkolfo I. Smani, Vasileios Megalooikonomou

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Social influence and influence diffusion have been studied in social networks. However, most existing tasks on this subject focus on static networks. In this paper, the problem of maximizing influence diffusion in dynamic social networks, i.e., the case of networks that change over time, is studied. The DM algorithm is an extension of the MATI algorithm and solves the influence maximization (IM) problem in dynamic networks and is proposed under the linear threshold (LT) and independent cascade (IC) models. Experimental results show that our proposed algorithm achieves a diffusion performance better by 1.5 times than several state-of-the-art algorithms and comparable results in diffusion scale with the Greedy algorithm. Also, the proposed algorithm is 2.4 times faster than previous methods.

Keywords: influence maximization, dynamic social networks, diffusion, social influence, graphs

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Authors: Esabella Yuan

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This study explored the recollections of young carers who lived with and cared for their mentally ill parent and how they managed life difficulties in Taiwan. 19 former young carers took part in the study, conducted from July to October 2021. The findings provided the unique view that all the participants acknowledged being taught by the mainstream culture to honour family value and prioritize the needs of parents over their own ones, they stepped in to care for the ill parent out of love and out of necessity through there having no-one to turn to, they were willing to assume long-term caring responsibilities, strikingly, a much more common experience was that the participants hided parental illness and young carer identity in the community through the fear of social discrimination attached to mental illness. As a result, these former young carers stayed in hidden circumstances and coped alone with caring challenges. The findings suggest that there needs multi-disciplinary services working together to recognize the needs of young carers and provide appropriate intervention to young carers based on a family-focus approach and ensure to serve the best interests of young carers and their families. It is to be hope that young carers can grow up safely and healthily within the community.

Keywords: young carers, family well-being, mental health, parental mental illness

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Authors: Swarna Pundir, Prabuddha Hans

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As AI has already stepped into the daily life of human society, one cannot be ignorant about the data it collects and used it to provide a quality of services depending up on the individuals’ choices. It also helps in giving option for making decision Vs choice selection with a calculation based on the history of our search criteria. Over the past decade or so, the way Artificial Intelligence (AI) has impacted society is undoubtedly large.AI has changed the way we shop, the way we entertain and challenge ourselves, the way information is handled, and has automated some sections of our life. We have answered as to what AI is, but not why one may see it as useful. AI is useful because it is capable of learning and predicting outcomes, using Machine Learning (ML) and Deep Learning (DL) with the help of Artificial Neural Networks (ANN). AI can also be a system that can act like humans. One of the major impacts be Joblessness through automation via AI which is seen mostly in manufacturing sectors, especially in the routine manual and blue-collar occupations and those without a college degree. It raises some serious concerns about AI in regards of less employment, ethics in making moral decisions, Individuals privacy, human judgement’s, natural emotions, biased decisions, discrimination. So, the question is if an error occurs who will be responsible, or it will be just waved off as a “Machine Error”, with no one taking the responsibility of any wrongdoing, it is essential to form some rules for using the AI where both machines and humans are involved.

Keywords: AI, ML, DL, ANN

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Authors: Marwa Hussien Mohamed, Mohamed Helmy Khafagy

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Map-Reduce is a programming model which is widely used to extract valuable information from enormous volumes of data. Map-reduce designed to support heterogeneous datasets. Apache Hadoop map-reduce used extensively to uncover hidden pattern like data mining, SQL, etc. The most important operation for data analysis is joining operation. But, map-reduce framework does not directly support join algorithm. This paper explains and compares two-way and multi-way map-reduce join algorithms for map reduce also we implement MR join Algorithms and show the performance of each phase in MR join algorithms. Our experimental results show that map side join and map merge join in two-way join algorithms has the longest time according to preprocessing step sorting data and reduce side cascade join has the longest time at Multi-Way join algorithms.

Keywords: Hadoop, MapReduce, multi-way join, two-way join, Ubuntu

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Authors: Yan Cheng, Yijun Shao, James Rudolph, Charlene R. Weir, Beth Sahlmann, Qing Zeng-Treitler

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Supervised predictive models require labeled data for training purposes. Complete and accurate labeled data, i.e., a ‘gold standard’, is not always available, and imperfectly labeled data may need to serve as an alternative. An important question is if the accuracy of the labeled data creates a performance ceiling for the trained model. In this study, we trained several models to recognize the presence of delirium in clinical documents using data with annotations that are not completely accurate (i.e., weakly-supervised learning). In the external evaluation, the support vector machine model with a linear kernel performed best, achieving an area under the curve of 89.3% and accuracy of 88%, surpassing the 80% accuracy of the training sample. We then generated a set of simulated data and carried out a series of experiments which demonstrated that models trained on imperfect data can (but do not always) outperform the accuracy of the training data, e.g., the area under the curve for some models is higher than 80% when trained on the data with an error rate of 40%. Our experiments also showed that the error resistance of linear modeling is associated with larger sample size, error type, and linearity of the data (all p-values < 0.001). In conclusion, this study sheds light on the usefulness of imperfect data in clinical research via weakly-supervised learning.

Keywords: weakly-supervised learning, support vector machine, prediction, delirium, simulation

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Authors: Arrian Cornwell, Larisa Yarovaya, Mary Thomson

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This paper seeks to examine the transboundary nature of foreign subsidiary exit vs. stay decisions when threatened by conflict in a host country. Using the concepts of nested vulnerability and teleconnections, we show that the threat of conflict can transcend bounded territories and have non-linear outcomes for actors, institutions and systems at broader scales of analysis. To the best of our knowledge, this has not been done before. By introducing the concepts of ‘leapfrogging upwards’ and ‘cascading downwards’, we develop a two-stage model which characterises the impacts of conflict as transboundary phenomena. We apply our model to a dataset of 266 foreign subsidiaries in six conflict-afflicted host countries over 2011-2015. Our results indicate that information is transmitted upwards and subsequent pressure flows cascade downwards, which, in turn, influence exit decisions.

Keywords: subsidiary exit, conflict, information transmission, pressure flows, transboundary

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Authors: M. Bruzza, M. Tupia, F. Rodríguez

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As part of the regulatory compliance process and the streamlining of public administration, the Peruvian government has implemented the National E-Government Plan in all state institutions with the aim of providing citizens with solid services based on the use of Information and Communications Technologies (ICT). As part of the regulations, the requisites to be met by public institutions have been submitted. However, the lack of an implementation model was detected, one that can serve as a guide to such institutions in order to materialize the organizational and technological structures needed, which allow them to provide the required digital services. This paper develops an implementation model of electronic government (e-government) for Peru’s state institutions, in compliance with current regulations based on a COBIT 5.0 framework. Furthermore, the paper introduces phase 1 of this model: business and IT goals, the goals cascade and the future model of processes.

Keywords: e-government, u-government, COBIT, implementation model

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Authors: Misbahuddin Mahammad, P. Chandra Sekhar, Metuku Shyamsunder

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The oversampled output of a sigma-delta modulator is decimated to Nyquist sampling rate by decimation filters. The decimation filters work twofold; they decimate the sampling rate by a factor of OSR (oversampling rate) and they remove the out band quantization noise resulting in an increase in resolution. The speed, area and power consumption of oversampled converter are governed largely by decimation filters in sigma-delta A/D converters. The scope of the work is to design a decimation filter for sigma-delta ADC and simulation using MATLAB. The decimation filter structure is based on cascaded-integrated comb (CIC) filter. A second decimation filter is using CIC for large rate change and cascaded FIR filters, for small rate changes, to improve the frequency response. The proposed structure is even more hardware efficient.

Keywords: sigma delta modulator, CIC filter, decimation filter, compensation filter, noise shaping

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Authors: Alexandre Gurchumelia, Luca Sorriso-Valvo, David Burgess, Khatuna Elbakidze, Oleg Kharshiladze, Diana Kvaratskhelia

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The terrestrial magnetosheath is a highly turbulent medium, with a high level of magnetic1field fluctuations throughout a broad range of scales. These often include an inertial range where a2magnetohydrodynamic turbulent cascade is observed. The multifractal properties of the turbulent3cascade, strictly related to intermittency, are observed here during the transition from quasi-parallel to4quasi-perpendicular magnetic field with respect to the bow-shock normal. The different multifractal5behavior in the two regions is analyzed. A standard coarse-graining technique has been used6to evaluate the generalized dimensions and the corresponding multifractal spectrumf(α). A7p-model fit provided a quantitative measure of multifractality and intermittency, to be compared with8standard indicators: the width of the multifractal spectrum, the peak of the kurtosis, and its scaling9exponent. Results show a clear transition and sharp differences in the intermittency properties for the two regions.

Keywords: magnetos heath, turbulence, multifractal, instabilities

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Authors: Ahmad Saadiq, Neeraj Sahu

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Sediment, which comprises of solid particles of mineral and organic material are transported by water. In river systems, the amount of sediment transported is controlled by both the transport capacity of the flow and the supply of sediment. The transport of sediment in rivers is important with respect to pollution, channel navigability, reservoir ageing, hydroelectric equipment longevity, fish habitat, river aesthetics and scientific interests. The sediment load transported in a river is a very complex hydrological phenomenon. Hence, sediment transport has attracted the attention of engineers from various aspects, and different methods have been used for its estimation. So, several experimental equations have been submitted by experts. Though the results of these methods have considerable differences with each other and with experimental observations, because the sediment measures have some limits, these equations can be used in estimating sediment load. In this present study, two black box models namely, an SRC (Sediment Rating Curve) and ANN (Artificial Neural Network) are used in the simulation of the suspended sediment load. The study is carried out for Seonath subbasin. Seonath is the biggest tributary of Mahanadi river, and it carries a vast amount of sediment. The data is collected for Jondhra hydrological observation station from India-WRIS (Water Resources Information System) and IMD (Indian Meteorological Department). These data include the discharge, sediment concentration and rainfall for 10 years. In this study, sediment load is estimated from the input parameters (discharge, rainfall, and past sediment) in various combination of simulations. A sediment rating curve used the water discharge to estimate the sediment concentration. This estimated sediment concentration is converted to sediment load. Likewise, for the application of these data in ANN, they are normalised first and then fed in various combinations to yield the sediment load. RMSE (root mean square error) and R² (coefficient of determination) between the observed load and the estimated load are used as evaluating criteria. For an ideal model, RMSE is zero and R² is 1. However, as the models used in this study are black box models, they don’t carry the exact representation of the factors which causes sedimentation. Hence, a model which gives the lowest RMSE and highest R² is the best model in this study. The lowest values of RMSE (based on normalised data) for sediment rating curve, feed forward back propagation, cascade forward back propagation and neural network fitting are 0.043425, 0.00679781, 0.0050089 and 0.0043727 respectively. The corresponding values of R² are 0.8258, 0.9941, 0.9968 and 0.9976. This implies that a neural network fitting model is superior to the other models used in this study. However, a drawback of neural network fitting is that it produces few negative estimates, which is not at all tolerable in the field of estimation of sediment load, and hence this model can’t be crowned as the best model among others, based on this study. A cascade forward back propagation produces results much closer to a neural network model and hence this model is the best model based on the present study.

Keywords: artificial neural network, Root mean squared error, sediment, sediment rating curve

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Authors: Zhai Yujia

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None of the scholars and researchers has ever stepped into this field, though there are quite a few papers worked on various topics relevant to cultural and economic globalization separately. Economic globalization is earlier than cultural globalization. Since the invention of currency, people have had the sense of making money for the purpose of living, supporting their families, or other personal reasons. Their strong desire for earning a living is one of the incentives to propel the trade, tourism and other related economic activities that provide the service within the homeland at first and expand into the whole world later, as the global markets grow and mature. The need for operation impels international communication or interaction. To achieve this, it is vital to realize or recognize other cultures to some degree, concluding language, customs, social etiquette and history of different nations. All this drives the cultural globalization process. In contrast, it is clear that the development of cultural globalization does accelerate the process of economic globalization in return. Under the guidance of Skopos theory (first proposed by Hans Vermeer, and its core principle is that the translation process is determined by the purpose), this paper aims to demonstrate that cultural globalization is not a process in isolation by analyzing its driving forces and retroaction thoroughly with an approach of overview. It intertwines with economic globalization. The two push each other to proper gradually during their development, serving as the indispensable parts of the globalization process.

Keywords: cultural globalization, driving forces, retroaction, Skopos theory

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Authors: Amel Ourici

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An electrical machine failure that is not identified in an initial stage may become catastrophic and it may suffer severe damage. Thus, undetected machine faults may cascade in it failure, which in turn may cause production shutdowns. Such shutdowns are costly in terms of lost production time, maintenance costs, and wasted raw materials. Doubly fed induction generators are used mainly for wind energy conversion in MW power plants. This paper presents a detection of an inter turn stator fault in a doubly fed induction machine whose stator and rotor are supplied by two pulse width modulation (PWM) inverters. The method used in this article to detect this fault, is based on Park’s Vector Approach, using a neural network.

Keywords: doubly fed induction machine, PWM inverter, inter turn stator fault, Park’s vector approach, neural network

Procedia PDF Downloads 579

Authors: M. Budakoglu, M. Karaman, D. Kiran, Z. Doner, B. Zeytuncu, B. Tanç, M. Kumral

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Lake Acıgöl is one of the large saline lacustrine environment in Turkey. Eleven trace metals (Cr, Mn, Fe, Al, Co, Ni, Cu, Zn, Cd, Pb and As) in 9 surface and subsurface sediment samples from the Lake Acıgöl were analyzed with the bulk and sequential extraction analysis methods by ICP-MS to obtain the metal distribution patterns in this extreme environment. Five stepped sequential extraction technique (1- exchangeable, 2- bond to carbonates, 3- bond to iron and manganese oxides/hydroxides, 4- bond to organic matter and sulphides, and 5- residual fraction incorporated into clay and silicate mineral lattices) was used to characterize the various forms of metals in the <63μ size sediments. The metal contents (ppm) and their percentages for each extraction step were reported and compared with the results obtained from the total digestion. Results indicate that sum of the four fraction are in good agreement with the total digestion results of Ni, Cd, As, Zn, Cu and Fe with the satisfactory recoveries (94.04–109.0%) and the method used is reliable and repeatable for these elements. It was found that there were high correlations between Fe vs. Ni loads in the fraction of F2 and F4 with R2= 0,91 and 0,81, respectively. Comparison of totally 135 chemical analysis results in three sampling location and for 5 fraction between Fe-Co, Co-Ni and Fe-Ni element couples were presented elevated correlations with R2=0,98, 0,92 and 0,91, respectively.

Keywords: Lake Acigol, sequancial extraction, recent lake sediment, geochemical speciation of heavy metals

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Authors: Malika Ourabia

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A new and efficient method is presented for the analysis of arbitrarily shaped discontinuities. The discontinuities is characterized using a hybrid spectral/numerical technique. This structure presents an arbitrary number of ports, each one with different orientation and dimensions. This article presents a hybrid method based on multimode contour integral and mode matching techniques. The process is based on segmentation and dividing the structure into key building blocks. We use the multimode contour integral method to analyze the blocks including irregular shape discontinuities. Finally, the multimode scattering matrix of the whole structure can be found by cascading the blocks. Therefore, the new method is suitable for analysis of a wide range of waveguide problems. Therefore, the present approach can be applied easily to the analysis of any multiport junctions and cascade blocks. The accuracy of the method is validated comparing with results for several complex problems found in the literature. CPU times are also included to show the efficiency of the new method proposed.

Keywords: segmentation, s parameters, simulation, optimization

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Authors: Kolade Olawande Owoeye, George Weir

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Terrorism and extremism activities on the internet are becoming the most significant threats to national security because of their potential dangers. In response to this challenge, law enforcement and security authorities are actively implementing comprehensive measures by countering the use of the internet for terrorism. To achieve the measures, there is need for intelligence gathering via the internet. This includes real-time monitoring of potential websites that are used for recruitment and information dissemination among other operations by extremist groups. However, with billions of active webpages, real-time monitoring of all webpages become almost impossible. To narrow down the search domain, there is a need for efficient webpage classification techniques. This research proposed a new approach tagged: SentiPosit-based method. SentiPosit-based method combines features of the Posit-based method and the Sentistrenght-based method for classification of terrorism and extremism webpages. The experiment was carried out on 7500 webpages obtained through TENE-webcrawler by International Cyber Crime Research Centre (ICCRC). The webpages were manually grouped into three classes which include the ‘pro-extremist’, ‘anti-extremist’ and ‘neutral’ with 2500 webpages in each category. A supervised learning algorithm is then applied on the classified dataset in order to build the model. Results obtained was compared with existing classification method using the prediction accuracy and runtime. It was observed that our proposed hybrid approach produced a better classification accuracy compared to existing approaches within a reasonable runtime.

Keywords: sentiposit, classification, extremism, terrorism

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Authors: M. Rajasekar, K. Suresh

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Diosmin is a flavonoid, most abundantly found in many citrus fruits. As a flavonoid, it possesses a multitude of biological activities including anti-hyperglycemic, anti-lipid peroxidative, anti-inflammatory, antioxidant, and anti-mutagenic properties. At this point, we established the anti-proliferative and apoptosis-inducing activities of diosmin in Hep-2 and KB cells. Diosmin has cytotoxic effects through inhibiting cellular proliferation of Hep-2 and KB cells, which leads to the induction of apoptosis, as apparent by an increase in the fraction of cells in the sub-G1phase of the cell cycle. Results exposed that inhibition of cell proliferation is associated with regulation of the Interleukins/STAT pathway. In addition, Diosmin treatment with Hep-2 and KB cells actively stimulated reactive oxygen species (ROS) and mitochondrial membrane depolarization. And also an imbalance in the Bax/Bcl-2 ratio triggered the caspase cascade and shifting the balance in favor of apoptosis. These observations conclude that Diosmin induce apoptosis via Interleukins /STAT-mediated pathway.

Keywords: diosmin, apoptosis, antioxidant, STAT pathway

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Authors: Mark Berry

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A number of studies have identified several factors involved in the malignant progression of cancer cells. The Primary modulator in driving inflammation to these transformed cells has been identified as the transcription factor known as nuclear factor-κB. This essential regulator of inflammation and the development of cancer, combined with a microenvironment of inflammation and signaling molecules, plays a major role in the malignant progression of cancer, and this progression is the result of the mutagenic predisposition of persistent substances that combat infection at tumor sites and other areas of chronic inflammation. Inflammation-induced tumors, and their inflammatory cells and regulators may be the primary source of metastasis of tumor cells through angiogenesis. Previous research on cytokines and chemokines, including their downstream targets, has been the focus of the cancer/inflammation connection. The identification of the biological mechanisms of other proteins vital to the inflammation cascade and their interactions are crucial to novel and effective therapeutic protocols for the treatment of inflammation-induced cancers. The Ancelim HSRP Protocol is just such a therapeutic intervention.

Keywords: ancelim, cancer, inflammation, tumor

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Authors: Hanan M. Hassan, Laila Abouzeid, Lamya H. Al-Wahaibi, George S. G. Shehatou, Ali A. El-Emam

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Cancer is a major public health problem and the second leading cause of death worldwide. In 2020, cancer diagnosis and treatment have been negatively affected by the coronavirus 2019 (COVID-19) pandemic. During the quarantine, because of the limited access to healthcare and avoiding exposure to COVID-19 as a contagious disease; patients of cancer suffered deferments in follow-up and treatment regimens leading to substantial worsening of disease, death, and increased healthcare costs. Thus, this study is designed to investigate the molecular mechanisms by which adamantne derivatives attenuate hepatocllular carcinoma experimentally and theoretically. There is a close association between increased resistance to anticancer drugs and defective apoptosis that considered a causative factor for oncogenesis. Cancer cells use different molecular pathways to inhibit apoptosis, BAX and Bcl-2 proteins have essential roles in the progression or inhibition of intrinsic apoptotic pathways triggered by mitochondrial dysfunction. Therefore, their balance ratio can promote the cellular apoptotic fate. In this study, the in vitro cytotoxic effects of seven synthetic adamantyl isothiorea derivatives were evaluated against five human tumor cell lines by MTT assay. Compounds 5 and 6 showed the best results, mostly against hepatocellular carcinoma (HCC). Hence, in vivo studies were performed in male Sprague-Dawley (SD) rats in which experimental hepatocellular carcinoma was induced with thioacetamide (TAA) (200 mg/kg, i.p., twice weekly) for 16 weeks. The most promising compounds, 5 and 6, were administered to treat liver cancer rats at a dose of 10 mg/kg/day for an additional two weeks, and the effects were compared with doxorubicin (DR), the anticancer drug. Hepatocellular carcinoma was evidenced by a dramatic increase in liver indices, oxidative stress markers, and immunohistochemical studies that were accompanied by a plethora of inflammatory mediators and alterations in the apoptotic cascade. Our results showed that treatment with adamantane derivatives 5 and 6 significantly suppressed fibrosis, inflammation, and other histopathological insults resulting in the diminished formation of hepatocyte tumorigenesis. Moreover, administration of the tested compounds resulted in amelioration of EGFR protein expression, upregulation of BAX, and lessening down of Bcl-2 levels that prove their role as apoptosis inducers. Also, the docking simulations performed for adamantane showed good fit and binding to the EGFR protein through hydrogen bond formation with conservative amino acids, which gives a shred of strong evidence for its hepatoprotective effect. In most analyses, the effects of compound 6 were more comparable to DR than compound 5. Our findings suggest that adamantane derivatives 5 and 6 are shown to have cytotoxic activity against HCC in vitro and in vivo, by more than one mechanism, possibly by inhibiting the TLR4-MyD88-NF-κB pathway and targeting EGFR signaling.

Keywords: adamantane, EGFR, HCC, apoptosis

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Authors: Tianjiao Chu, Carla Rios Luci, Christy Maksoudian, Ara Sargsian, Bella B. Manshian, Stefaan J. Soenen

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Nanomaterials have gained high interest in their use as potent anticancer agents. Apart from delivering chemotherapeutic agents in order to reduce off-target effects, molecular agents have also been widely explored. The advances in our understanding of cell biology and cell death mechanisms1 has generated a broad library of potential therapeutic targets by siRNA, mRNA, or pDNA complexes. In the present study, we explore the ability of pDNA-polyplexes to induce tumor-specific necroptosis. This results in a cascade of effects, where immunogenic cell death potentiates anti-tumor immune responses and results in an influx of dendritic cells and cytotoxic T cells, rendering the tumor more amenable to immune checkpoint inhibition. This study aims to explore whether the induction of necroptosis in a subpopulation of tumor cells can be used to potentiate immune checkpoint inhibition studies.

Keywords: nanoparticle, MLKL, necroptosis, immunotherapy

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Authors: Margarita Ivanova, Julia Dao, Andrew Friedman, Neil Kasaci, Rekha Gopal, Ozlem Goker-Alpan

Abstract:

In Fabry disease (FD), α-galactosidase A (α-Gal A) deficiency leads to the accumulation of globotriaosylceramide (Lyso-Gb3 and Gb3), triggering a pathologic cascade that causes the severity of organs damage. The heart is one of the several organs with high sensitivity to the α-Gal A deficiency. A subgroup of patients with significant residual of α-Gal A activity with primary cardiac involvement is occasionally referred to as “cardiac variant.” The cardiovascular complications are most frequently encountered, contributing substantially to morbidity, and are the leading cause of premature death in male and female patients with FD. The deposition of Lyso-Gb-3 and Gb-3 within the myocardium affects cardiac function with resultant progressive cardiovascular pathology. Gb-3 and Lyso-Gb-3 accumulation at the cellular level trigger a cascade of events leading to end-stage fibrosis. In the cardiac tissue, Lyso-Gb-3 deposition is associated with the increased release of inflammatory factors and transforming growth factors. Infiltration of lymphocytes and macrophages into endomyocardial tissue indicates that inflammation plays a significant role in cardiac damage. Moreover, accumulated data suggest that chronic inflammation leads to multisystemic FD pathology even under enzyme replacement therapy (ERT). NF-κB activation plays a subsequent role in the inflammatory response to cardiac dysfunction and advanced heart failure in the general population. TNFalpha/NF-κB signaling protects the myocardial evoking by ischemic preconditioning; however, this protective effect depends on the concentration of TNF-α. Thus, we hypothesize that TNF-α is a critical factor in determining the grade of cardio-pathology. Cardiac hypertrophy corresponds to the expansion of the coronary vasculature to maintain a sufficient supply of nutrients and oxygen. Coronary activation of angiogenesis and fibrosis plays a vital role in cardiac vascularization, hypertrophy, and tissue remodeling. We suggest that the interaction between the inflammatory pathways and cardiac vascularization is a bi-directional process controlled by secreted cytokines and growth factors. The co-coordination of these two processes has never been explored in FD. In a cohort of 40 patients with FD, biomarkers associated with inflammation and cardio hypertrophic remodeling were studied. FD patients were categorized into three groups based on LVmass/DSA, LVEF, and ECG abnormalities: FD with no cardio complication, FD with moderate cardio complication, and severe cardio complication. Serum levels of NF-kB, TNFalpha, Il-6, Il-2, MCP1, ING-gamma, VEGF, IGF-1, TGFβ, and FGF2 were quantified by enzyme-linked immunosorbent assays (ELISA). Among the biomarkers, MCP-1, INF-gamma, VEGF, TNF-alpha, and TGF-beta were elevated in FD patients. Some of these biomarkers also have the potential to correlate with cardio pathology in FD. Conclusion: The study provides information about the role of inflammatory pathways and biomarkers of cardio hypertrophic remodeling in FD patients. This study will also reveal the mechanisms that link intracellular accumulation of Lyso-GB-3 and Gb3 to the development of cardiomyopathy with myocardial thickening and resultant fibrosis.

Keywords: biomarkers, Fabry disease, inflammation, growth factors

Procedia PDF Downloads 67

Authors: Madeline Foster

Abstract:

Since the COVID-19 pandemic, telehealth usage for the delivery of psychotherapy has surged. The evidence base evaluating the success of telehealth interventions continues to grow, with both benefits as well as potential risks identified. This study compared two recent randomized clinical trials (RCTs) from Sweden that looked at the effectiveness of Cognitive Behavioral Therapy (CBT) delivered via telehealth (TH) versus face-to-face (FTF) for individuals with Obsessive Compulsive Disorder (OCD). The papers had mixed results. The first paper by Aspvall and colleagues compared the effect of a therapist-supported, internet-delivered stepped-care CBT program for children and adolescents aged 7 to 17 with face-to-face CBT (2021). In Aspvall’s study, the control scored a mean Y-BOCS of 10.57 and the TH intervention group scored a mean Y-BOCS of 11.57. The mean difference (0.91) met the criteria for noninferiority (p = 0.03). The second study by Lundström and colleagues also compared therapist-supported, internet-based CBT with FTF CBT for the treatment of those with DSM-5-diagnosed OCD. Conversely, while Lundström’s study reported improved symptoms across all groups, at follow up the difference in symptom severity between FTF and TH was clinically significant, with 77% of FTF participants responding to treatment compared to only 45% of TH participants. Due to the methodological limitations of Lundström’s study, it was concluded that Aspvall’s paper made a stronger scientific argument.

Keywords: telehealth, Sweden, RCT, cognitive-behavioral therapy, obsessive-compulsive disorder

Procedia PDF Downloads 49

Authors: Nick Weir, Robert Stevens, Alan Hargreaves, Martin McGinnity, Chris Tinsley

Abstract:

Hydrophobic materials have previously demonstrated the ability to elevate cell-cell interactions and promote the formation of neural networks whilst aligned nanofibers demonstrate the ability to induce extensive neurite outgrowth in an aligned manner. Hydrophobic materials typically elicit an immune response upon implantation and thus materials used for implantation are typically hydrophilic. Poly-L-lactic acid (PLLA) is a hydrophobic, non-immunogenic, FDA approved material that can be electrospun to form aligned nanofibers. Primary rat cortical neurons cultured for 10 days on aligned PLLA nanofibers formed 3D cell clusters, approximately 800 microns in diameter. Neurites that extended from these clusters were highly aligned due to the alignment of the nanofibers they were cultured upon and fasciculation was also evident. Plasma treatment of the PLLA nanofibers prior to seeding of cells significantly reduced the hydrophobicity and abolished the cluster formation and neurite fasciculation, whilst reducing the extent and directionality of neurite outgrowth; it is proposed that hydrophobicity induces the changes to cellular behaviors. Aligned PLLA nanofibers induced the formation of a structure that mimics the grey-white matter compartmentalization that is observed in vivo and thus represents a step forward in generating organoids or biomaterial-based implants. Upon implantation into the brain, the biomaterial architectures described here may provide a useful platform for both brain repair and brain remodeling initiatives.

Keywords: hydrophobicity, nanofibers, neurite fasciculation, neurite outgrowth, PLLA

Procedia PDF Downloads 137